文章基本信息

标题：Spontaneous generation of anchorless prions in transgenic mice
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作者：Jan Stöhr ; Joel C. Watts ; Giuseppe Legname 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2011
卷号：108
期号：52
页码：21223-21228
DOI：10.1073/pnas.1117827108
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Some prion protein mutations create anchorless molecules that cause Gerstmann-Straussler-Scheinker (GSS) disease. To model GSS, we generated transgenic mice expressing cellular prion protein (PrPC) lacking the glycosylphosphatidyl inositol (GPI) anchor, denoted PrP({Delta}GPI). Mice overexpressing PrP({Delta}GPI) developed a late-onset, spontaneous neurologic dysfunction characterized by widespread amyloid deposition in the brain and the presence of a short protease-resistant PrP fragment similar to those found in GSS patients. In Tg(PrP,{Delta}GPI) mice, disease onset could be accelerated either by inoculation with brain homogenate prepared from spontaneously ill animals or by coexpression of membrane-anchored, full-length PrPC. In contrast, coexpression of N-terminally truncated PrP({Delta}23-88) did not affect disease progression. Remarkably, disease from ill Tg(PrP,{Delta}GPI) mice transmitted to mice expressing wild-type PrPC, indicating the spontaneous generation of prions.
关键词：protein misfolding ; amyloidosis ; neurodegenerative disease ; proteinopathies